Beyond Biology: Autoimmune Illnesses and the Big Unknown

Autoimmune illnesses are remarkably common and debilitating, yet we know almost nothing about them.
Jenn Halweil

In Ancient Greece, it was thought that the uterus could wander around the body, searching feverishly for sperm in an effort to become pregnant. 

Sometimes the womb would get a bit lost. 

When that happened, it was said to cast horrible afflictions upon an individual. Should the uterus find its way to the ribcage, the patient may feel shortness of breath or chest pains. Should it reach the head, they may develop a migraine or headache. 

The cure for this jack-of-all-trades ailment? Pregnancy. If the oh-so-hungry womb could find sperm and latch onto a child, it would no longer have the need to wander about, freeing the afflicted from any woes. 

In the following millennia, women were thought to be especially prone to "hysteria" (the word is derived from the Greek hystera, or uterus), which became a catch-all name for any physical problems suffered by women that did not have an obvious cause, from depression to migraines to being too "emotional". Hysteria was considered, largely, a uniquely female affliction. From the days of the wandering womb to Freud’s ideas that the desire for a penis was the root of women's mental health issues, men were rarely diagnosed with hysteria, although it started to become a slightly more common diagnosis in men toward the end of the 19th century. Largely, hysteria was treated with methods that had no clinical value, and could often be harmful. Charlotte Perkins Gilman’s The Yellow Wallpaper captivated audiences with its fictional (but often considered semi-autobiographical) account of a woman’s treatment for what we now know as postpartum depression, but was then diagnosed as "hysteria". Her treatment included being forbidden from working or writing. It wasn’t until 1980 that hysteria was removed from the Diagnostic and Statistical Manual of Mental Disorders (DSM).

The diagnosis of hysteria might not be around anymore, but the treatment of illnesses that predominantly affect women remains somewhat muddled. One of the most serious of these issues is in the diagnosis and treatment of autoimmune diseases.

Autoimmune diseases, such as rheumatoid arthritis (RA) and psoriasis, occur when the body’s immune system attacks itself. Over 24 million people in the United States alone have at least one of the more than 100 identified autoimmune diseases, with many having multiple different illnesses.

Does gender play into our understanding of autoimmune illness?

More than 80T% of all autoimmune patients are women, and are a leading cause of death and disability in women aged 15 to 44 years.

These illnesses are disproportionately diagnosed in women: Rheumatoid arthritis affects three times more women than men; systemic lupus erythematosus (SLE), the most common type of lupus, affects seven times more women than men; and Sjorgen’s syndrome affects nine times more women than men. 

For a long time, and continuing today, symptoms of autoimmune illnesses in women were overlooked or seen as an exaggeration — an extension of the belief in women's "hysteria". In an interview with iNews UK, Physician Professor Julia Newton, who specializes in fatigue, said: “I wasn’t taught about ME [an autoimmune illness that causes chronic fatigue] when I was at medical school. Even now, it’s very poorly understood, and very infrequently recognized as a genuine biological condition. Patients are misunderstood and not believed. The belief that ME is psychological, rather than a physical illness, has held the field back for years — and that may partly be because it’s a female dominant condition. Sufferers are seen as ‘hysterical’.”

Despite the seriousness and frequency of these illnesses, we know relatively little about most of them. To this day, the exact cause of the autoimmune disease remains murky; the general scientific consensus is that it’s some mixture of hormonal, genetic, and environmental factors. For example, smoking tobacco has been linked to the development of systemic lupus erythematosus and rheumatoid arthritis. In individuals who already have a genetic predisposition to the disease, smoking further compounds the odds of a diagnosis. Researchers have also postulated that autoimmune diseases may be associated with the X chromosome. Because women normally have two X chromosomes, they have a higher risk of autoimmune diseases, as compared to men. 

In a 2020 study, researchers found that a number of autoimmune illnesses that disproportionately affect women, such as RA and multiple sclerosis (MS), are underfunded relative to the severity and burden of the disease. This perpetuates a negative cycle regarding the lack of knowledge around autoimmune illness: with little funding, research is like looking for a needle in a haystack, when we have no idea what the needle even looks like. 

It's hard to get a diagnosis

Diagnosing and treating autoimmune illnesses in the first place can be an extremely difficult endeavor. On average, patients visit six doctors over the course of four years before they receive a diagnosis. Since many autoimmune diseases share symptoms, trying to distinguish between different diseases can be difficult, and at times even impossible. Additionally, if symptoms are too “mild”, patients may be discounted as exaggerating (the old issue of hysteria again) and need to wait years before more “intense” symptoms develop to receive a proper diagnosis. Even in some of the most common ailments, like RA or lupus, there are often no effective treatments for the disease itself. Instead, treatment focuses more on alleviating symptoms as opposed to curing a disease. 

Many patients have grown desperate as a result of the lack of information. This has caused a dramatic growth in the use of public forums like Facebook, Reddit, and Quora to find diagnoses and treatments. On sites like Facebook, members of groups track all of their symptoms for extended periods of time and post them, hoping that someone else can identify what they’ve gone through and provide a helping hand. These groups have significant traction: over 38,000 people follow Facebook’s Lupus Support Page, and more than 10,000 follow Facebook’s Crohn's Disease Support Community. These social media pages are helping people “biohack” their disease and crowdsource medical data — they’re creating new places to get help and identify new methods to treat their disease, including holistic approaches. 

Biohacking and crowdsourcing

One innovation in autoimmune disease is taking a more “old school” approach toward treating the illnesses — using arsenic salts. Despite its scary and deadly reputation, arsenic has a long history of use in the apothecary, and not just for offing a spouse or two in the olden days. Before antibiotics became available, it was a common treatment for syphilis, and is still a highly effective medicine against some forms of leukemia. In 2015, researchers from Medsenic found that arsenic trioxide was a safe and effective lupus treatment, and suggested that additional study should be made into its use as a possible treatment. The findings also spurred a further investigation into the effects of arsenic on chronic graft-versus-host disease (cGvHD), an autoimmune disorder in which transplanted cells, such as bone marrow cells, attack a patient’s healthy, non-transplanted cells. Preliminary results have shown that the treatment has had significant results thus far.

As autoimmune illnesses are becoming more common, more researchers have begun chasing cures. One of the most promising treatments is gene therapy. Gene therapy targets the genes within the body that cause disease. For example, gene therapy for some autoimmune conditions could target cytokines, a protein in the immune system, that promote inflammation in the body. 

But much like our understanding of hysteria, autoimmune illness, and female healthcare, our understanding of genetics developed a great deal over time. It initially grew out of discoveries focused on inheritance of traits by Czech mathematician, biologist, and friar Gregor Mendel. In 1905, biologist William Bateson was the first person to use the term “genetics to describe the study of heredity. Throughout the early 20th century, the study of genetics included the darker notions of the eugenics movement and the concept that undesirable traits could be bred out of the human race through selective breeding and sterilization. This misunderstanding of genetics ultimately contributed to Nazism’s concept of the “ideal” Aryan race, which has thankfully since been condemned. 

Many genomic medical breakthroughs involved the work of the Human Genome Project, which originally worked to map the approximately 20,500 unique human genes, and continues the work today by mapping the complete genome of other organisms. Gene editing breakthroughs like CRISPR hold out the promise of being able to selectively edit genes in order to eliminate the causes of some diseases. For example, researchers have already used CRISPR techniques to control the ILRA (Interleukin 2 alpha) protein, which signals to T cells whether they should heighten or dampen an inflammatory response. In the future, this could allow doctors to treat autoimmune diseases by turning off the inflammatory response when it has gone out of control.

Scientists and medical care providers are also increasingly recognizing the role of epigenetics — the study of how genetic and environmental factors combine to cause changes that affect genes — to establish more effective treatment protocols and even cures. It seems that in immunology, at least, the answer to the age-old question of nature vs. nurture is likely “both.” 

For example, for decades, ulcers were thought to be caused by stress, a simple factor that could generally be controlled. However, in 1985, Australian researchers Barry J. Marshall and Robin Warren decided to investigate the role of the bacteria Helicobacter pylori in ulcer development — even going so far as to have Marshall ingest the bacteria. When he developed ulcers, the two proved the role of infection in developing ulcers, which went against all previous medical beliefs in this area, and earned them the Nobel Prize. 

The challenge is that many autoimmune treatment studies use small sample sizes and produce mixed results, in part because most therapies target the symptoms, instead of the root cause of the illness. Of course, this is because it is far simpler to target a small number of genes instead of trying to correct for a huge number of unknown environmental factors. 

The world of autoimmune diseases may still be murky, but we’re learning more and more every day. Thankfully, gone are the days when your doctor would suggest that your heart murmur was caused by your uterus wandering up to your chest or cure your hysteria with a vibrator. But until we take women's health issues as seriously as men's and dedicate more research money and time in investigating autoimmune diseases, here’s to hoping greater data sharing and investment in research will uncover better treatment options. 

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